daf-2;oga-1

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

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Locus: CELE_Y55D5A.5

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Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

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O-GlcNAc selective N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase)

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Locus: CELE_T20B5.3

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Wormbase description: oga-1 encodes an ortholog of mammalian O-linked N-acetylglucosamine (O-GlcNAc)-selective N-acetyl-beta-D-glucosaminidase (O-GlcNAcase); a polymorphism of OGA-1's human ortholog MGEA5 is associated with type 2 diabetes, and OGA-1 appears to be required for fine-tuning of insulin signalling; oga-1(ok1207) mutants are viable and fertile but accumulate O-GlcNAc on nuclear pores and other proteins, while showing S/T-phosphorylation of proteins, increased GSK-3beta activity, excess glycogen and trehalose, and decreased lipid storage; oga-1(ok1207) mutations enhance the Daf-c phenotype of daf-2(e1370ts) alleles even under conditions where oga-1(ok1207) alone diminishes dauer formation.

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